A. Role of cAMP in mediating gastrointestinal smooth muscle relaxation by beta-adrenergic agents or neuropeptides. It has been suggested but not proven that cAMP is an essential mediator of relaxation by these agents in GI smooth muscle. To investigate the role of cAMP in relaxation, in this study in dispersed gastric smooth muscle cells, the effect of the competitive protein kinase A antagonist (Rp-cAMPS) was investigated. The results demonstrated the activation of PKA is primarily responsible for mediating gastric smooth muscle relaxation produced by these agents. B. Action of somatostatin on gastric smooth muscle. Somatostatin has potent effects on GI motility as well as gastric motility. To determine whether somatostatin can interact directly with GI smooth muscle cells, in this study the ability of various somatostatins to interact with gastric smooth muscle cells prepared from guinea pig stomach was examined. The results demonstrated smooth muscle cells possess high affinity somatostatin (SS) receptors. Smooth muscle cells rapidly degrade SS-14, but not SS-28 or a synthetic SS-8 analogue and this may be a major determinant of biologic activity. Somatostatin had no effect alone, but inhibited relaxants. The inhibitory effect was mediated both through a guanine nucleotide regulatory protein to inhibit adenylate cyclase and at a site distal to the generation of cAMP. C. Characterization of opoiod receptors on gastric smooth muscle. Numerous neural elements in the GI tract possess receptors for opoiod peptides and some recent studies suggest that GI smooth muscle also possess opoiod receptors. In this study specific opoiod ligands as well as selective agonists and antagonists were used to study opoiod receptors on gastric smooth muscle cells. The results demonstrated these GI smooth muscle cells possessed k and mu opoiod receptors but no delta receptors and that occupation of either the k or mu receptor results in muscle contraction, therefore opoiod peptides interacting with these receptors can possibly alter motility by interacting directly with smooth muscle cells.